Browsing by Author "Silva, Ana Isabel"
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- Astrocyte-derived TNF and glutamate critically modulate microglia activation by methamphetaminePublication . Canedo, Teresa; Portugal, Camila Cabral; Socodato, Renato; Almeida, Tiago Oliveira; Terceiro, Ana Filipa; Bravo, Joana; Silva, Ana Isabel; Magalhães, João Duarte; Guerra-Gomes, Sónia; Oliveira, João Filipe; Sousa, Nuno; Magalhães, Ana; Relvas, João Bettencourt; Summavielle, TeresaMethamphetamine (Meth) is a powerful illicit psychostimulant, widely used for recreational purposes. Besides disrupting the monoaminergic system and promoting oxidative brain damage, Meth also causes neuroinflammation, contributing to synaptic dysfunction and behavioral deficits. Aberrant activation of microglia, the largest myeloid cell population in the brain, is a common feature in neurological disorders triggered by neuroinflammation. In this study, we investigated the mechanisms underlying the aberrant activation of microglia elicited by Meth in the adult mouse brain. We found that binge Meth exposure caused microgliosis and disrupted risk assessment behavior (a feature that usually occurs in individuals who abuse Meth), both of which required astrocyte-to-microglia crosstalk. Mechanistically, Meth triggered a detrimental increase of glutamate exocytosis from astrocytes (in a process dependent on TNF production and calcium mobilization), promoting microglial expansion and reactivity. Ablating TNF production, or suppressing astrocytic calcium mobilization, prevented Meth-elicited microglia reactivity and re-established risk assessment behavior as tested by elevated plus maze (EPM). Overall, our data indicate that glial crosstalk is critical to relay alterations caused by acute Meth exposure.
- Deciphering the astrocytic and synaptic changes under chronic alcohol exposure using a self-administration paradigmPublication . Rodrigues, Ana Margarida; Canedo, Teresa; Terceiro, Ana Filipa; Tedim-Moreira, Joana; Silva, Ana Isabel; Magalhães, Ana; Relvas, João; Summavielle, TeresaDrug abuse is characterized by a compulsive and persistent drug-seeking behaviour, despite the harmful emotional, physical and social consequences. Our laboratory has previously found that the neuronal-glial crosstalk is critical in relaying the changes caused by acute exposure to psychoactive drugs through neuroimmune mechanisms. We have also reported that microglia can engulf postsynaptic components in the prefrontal cortex (PFC) of mice after repeated alcohol exposure and this led to increased anxiety in mice. The adverse effects of alcohol on the central nervous system (CNS) are well described, with astrocytes becoming reactive and displaying changes in gene expression, activity and proliferation. However, the mechanisms involved are not yet fully understood. We are currently characterizing the astrocytic response under chronic alcohol consumption, taking into account the crucial interaction between neuronal and glial cells in the development and maintenance of addiction. Using a well-established voluntary alcohol drinking paradigm, we are evaluating alcohol-associated changes in PFC astrocytes, synapses and their behavioural correlates. Our preliminary results indicate similar alcohol consumption patterns between males and females, however, males, but not females, present altered weight gain and experience a significant increase in inhibitory synapse density after chronic exposure to ethanol when compared to the control group. Our work is contributing to a better understanding of the impact of chronic alcohol intake and may lead to the development of new strategies for pharmacological intervention in drug addiction, based on the targets identified as critical for the neuronal-glial crosstalk.
- IL-10 and Cdc42 modulate astrocyte-mediated microglia activation in methamphetamine-induced neuroinflammationPublication . Silva, Ana Isabel; Socodato, Renato; Pinto, Carolina; Terceiro, Ana Filipa; Canedo, Teresa; Relvas, João Bettencourt; Saraiva, Margarida; Summavielle, TeresaMethamphetamine (Meth) use is known to induce complex neuroinflammatory responses, particularly involving astrocytes and microglia. Building upon our previous research, which demonstrated that Meth stimulates astrocytes to release tumor necrosis factor (TNF) and glutamate, leading to microglial activation, this study investigates the role of the anti-inflammatory cytokine interleukin-10 (IL-10) in this process. Our findings reveal that the presence of recombinant IL-10 (rIL-10) counteracts Meth-induced excessive glutamate release in astrocyte cultures, which significantly reduces microglial activation. This reduction is associated with the modulation of astrocytic intracellular calcium (Ca2+) dynamics, particularly by restricting the release of Ca2+ from the endoplasmic reticulum to the cytoplasm. Furthermore, we identify the small Rho GTPase Cdc42 as a crucial intermediary in the astrocyte-to-microglia communication pathway under Meth exposure. By employing a transgenic mouse model that overexpresses IL-10 (pMT-10), we also demonstrate in vivo that IL-10 prevents Meth-induced neuroinflammation. These findings not only enhance our understanding of Meth-related neuroinflammatory mechanisms, but also suggest IL-10 and Cdc42 as putative therapeutic targets for treating Meth-induced neuroinflammation.
- Motivation as a lever for service excellencePublication . Silva, Ana Isabel; Oliveira, Mónica; Silva, SusanaIn recent years, we have seen a change in mentalities in the way organisations are managed. Day by day, we realize that an organization's human resources are the key to success. In this sense, human resources management assumes an essential position that will allow to achieve levels of motivation and satisfaction of employees central to the performance of the organization. In the hotel sector, we still observe organizations with little focus on human resources management. However, it is from the sectors where this management becomes vital. The satisfaction and motivation of employees are directly reflected in customer satisfaction, compromising the future of the hotel unit. This work aims to understand the impact of the employee's motivation on their performance, according to their perspective. Thus, the method used was the questionnaire survey, addressed to all employees of the InterContinental Porto — Palácio das Cardosas hotel. Data analysis was performed through descriptive and statistical analysis, with resources to the SPSS (Statistical Package for Social Sciences) program. The results obtained did not allow us to observe any direct relationship between employee motivation and performance, according to their perspective.
- Repeated exposure to ketamine in adolescent rats results in persistent anxiety in the adulthoodPublication . Amorim, Manuela; Bravo, Joana; Silva, Ana Isabel; Alves, Cecília Juliana; Monteiro, Pedro; Magalhãess, Ana; Summavielle, TeresaAdolescent development of the prefrontal cortex (PFC) is accompanied by important changes in glutamatergic, GABAergic and dopaminergic circuitries, susceptible to modulation by N-methyl-D-aspartate receptors (NMDAR) antagonists. Repeated ketamine was associated with social and memory deficits, but other relevant factors, such as anxiety, were not sufficiently addressed. The present study aimed to examine the behavioral and molecular consequences of repeated exposure to ketamine with a particular focus in anxiety. Methods. We treated male adolescent Wistar rats, starting postnatal day (PND) 35, with ketamine (30 mg/kg, i.p, 7 days). Behavioral evaluation was conducted in the adulthood (PND 60). The elevated plus maze (EPM) and open field tests were used to evaluate anxiety and locomotion, while sociability and novelty recognition were assessed through the novel object recognition (NOR) and the sociability and social novelty tests. At the end of the behavioral evaluation, brains were dissected and the prefrontal cortex used for biochemical evaluation. Results. Analysis of the elevated plus maze (EPM) data revealed a ketamine-induced anxiety-like profile, corroborated by the open field data. Ketaminetreated rats also failed to increase contact time with a conspecific in the social affiliation test and with an unknown rat in the novelty preference test. At the molecular level, frontal expression levels of tyrosine hydroxylase were found decreased. Conclusion. Altogether, these results show that repeated ketamine-exposure in the adolescent may result in long-term anxiety